Circulating Biomarkers and Targeted Therapy in Pleural Mesothelioma

Our plain-English summary of Circulating Biomarkers and Targeted Therapy in Pleural Mesothelioma, by C.R. Grant, L. Bazhenova, K.M. Yun (Cancers, 2025).

The study

• Authors: C.R. Grant, L. Bazhenova, K.M. Yun
• Journal: Cancers
• Published: 2025;17(23)
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a rare and aggressive cancer. Standard of care for unresectable disease consists of chemotherapy, vascular endothelial growth factor inhibition, immunotherapy, or combinations thereof. Despite recent therapeutic advances, validated diagnostic and prognostic biomarkers are lacking, and no targeted therapies have been approved by the U.S. Food and Drug Administration (FDA) to date. Given the growing body of research investigating molecular alterations in PM, this review summarizes emerging diagnostic and prognostic biomarkers, discusses potentially targetable molecular alterations, and examines ongoing trials directed at targeting specific molecular mechanisms in this disease.

In plain English

This article was a review, not a new study. The authors, from UC San Diego, searched PubMed, ClinicalTrials.gov and Google Scholar for studies of blood and pleural-fluid markers (biomarkers) for pleural mesothelioma and for trials of targeted drugs, and summarized what those studies reported. They noted that soluble mesothelin-related protein (SMRP) is the only biomarker approved by the U.S. FDA for mesothelioma, and only for monitoring treatment response, not for diagnosis. They cited a pooled analysis of 16 studies in which serum mesothelin had an average sensitivity of 47% and specificity of 96%. They also reported that several prospective studies failed to show a benefit of serum mesothelin or SMRP as screening tools in people with occupational asbestos exposure. Among targeted drugs, they described mesothelin-targeted therapies as the most studied yet unsuccessful, and PARP inhibitors as showing limited efficacy in BAP1-negative patients. One cited randomized trial in 249 untreated non-epithelioid patients reported a longer median overall survival with ADI-PEG20 plus chemotherapy than with chemotherapy alone (9.3 vs. 7.7 months). The authors concluded that no circulating marker had enough evidence for FDA approval as a diagnostic biomarker, and that no targeted therapy is approved.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies and registered clinical trials on circulating biomarkers and targeted therapies in pleural mesothelioma
• Who was studied: Prospective and retrospective studies of diagnostic, prognostic and predictive circulating biomarkers for pleural mesothelioma, plus prospective studies and ongoing trials of targeted therapies, found through PubMed, ClinicalTrials.gov and Google Scholar. No search dates or number of included studies are given.
• Exposure: No asbestos exposure was studied. The review covered circulating biomarkers (mesothelin/SMRP, megakaryocyte potentiating factor, fibulin-3, HMGB1, CD157, circulating tumor DNA, calretinin, microRNAs, CYFRA 21-1, activin A, podoplanin, KL-6, eosinophils) and targeted therapies (against mesothelin, BAP1, NF2, CDKN2A, MTAP, AXL, ASS1, WT1).
• Main results:
  • The review stated that SMRP is the only FDA-approved biomarker for mesothelioma, authorized for treatment response monitoring but not for diagnosis.
  • A cited meta-analysis of 16 studies of serum mesothelin, recalculated at a threshold of 2.00 nmol/L, found an average sensitivity of 47% (range 19% to 68%) and an average specificity of 96% (range 88% to 100%).
  • The review reported that several prospective studies failed to show a benefit of serum mesothelin or SMRP as screening tools in individuals with occupational asbestos exposure.
  • A cited prospective study of individuals with a long history of asbestos industry exposure in southeast China reported serum HMGB1 sensitivity of 100% and specificity of 80.28% at a cutoff of 52.16 ng/mL.
  • In the cited ATOMIC-meso trial of 249 treatment-naive non-epithelioid pleural mesothelioma patients, ADI-PEG20 plus chemotherapy was reported to give longer median progression-free survival (6.2 vs. 5.6 months; HR 0.65) and median overall survival (9.3 vs. 7.7 months; HR 0.71) than chemotherapy alone.
  • In cited phase II data on VT3989, the overall response rate was 32% among 22 mesothelioma patients treated at optimized doses. The review noted that a separate result for pleural mesothelioma patients had not yet been reported.
  • The authors summarized that PARP inhibitors largely showed limited efficacy in BAP1-negative patients.
  • The authors summarized that mesothelin-targeted therapies were the most heavily studied, yet unsuccessful.
• The authors' conclusion: The authors concluded that no circulating marker has shown enough evidence for FDA approval as a diagnostic biomarker for pleural mesothelioma, that existing biomarkers lack the needed sensitivity and specificity, especially for early-stage disease and non-epithelioid subtypes, and that no targeted therapy is currently approved, although research is ongoing.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Targeted Therapy, Pleural Mesothelioma, Unresectable, Chemotherapy, Immunotherapy.

Related studies

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• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)
• Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma — B. Ghanim, M.A. Hoda, et al. (2014)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation — L. Ferrari, M. Carugno, et al. (2020)
• A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma — B.T.V. Duong, L. Wu, et al. (2020)

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